UAMS researcher Robert J. Griffin on the biology of experimental therapeutics and targeted radiation strategies for solid tumors.
By BECKY GILLETTE
Robert J. Griffin, PhD, a professor of radiation and cancer biology in the University of Arkansas for Medical Sciences (UAMS) Department of Radiation Oncology, finds this an exciting time to be involved in nanomedicine, the use of extremely small particles to deliver nanoliposomes and different types of nanomedicines directly to tumor cells and tumor tissue to avoid damage from radiation, chemotherapy or thermal treatment in healthy cells and tissues. Griffin has authored nearly 150 peer-reviewed articles on the biology of experimental therapeutics and targeted radiation strategies for solid tumors.
Griffin is currently teaming up with a small startup company, Rejuvenix Technologies, LLC, at the UAMS business incubator in Little Rock to help develop patents for radiation-triggered drug release from lipid-based carriers for cancer. A $383,213 National Cancer Institute (NCI) Small Business Innovation Research Phase I contract was awarded to develop encapsulated radiation-triggered liposomes intended to achieve safer, controlled delivery of chemotherapy. The technology has the potential to improve clinical outcomes for cancer patients by reducing side effects while increasing effectiveness of certain drugs that would be part of a normal mixture of various chemotherapy agents, depending on the cancer type and stage.
“It is exciting to be involved with radiation drug-release nanoparticle therapy,” Griffin said. “Messenger RNA Covid vaccines are lipid-based nanoparticles. We have really got acceptance with our lipid-based drug-delivery nanoparticles.”
As part of his research effort and a business development program offered by the NCI, Griffin talked to over 100 experts in the oncology arena and found they are desperate to deliver chemotherapies that are already FDA approved more selectively and effectively in a variety of contexts.”
“When patients are flooded with chemotherapy, they are indiscriminately being exposed to high drug levels all over the body and can have a rough go of it,” Griffin said. “The chemotherapy works to kill cancer cells in the primary tumor or those that might be spread to other organs--but comes at a terrible cost. Everything seems advanced these days, but we are still using many chemotherapy treatments that are decades old. UAMS and Rejuvenix have interesting potential to help oncologists do a better job helping patients. After talking to the physicians administering these drugs, we learned a lot. A new approach administering one or more of the drugs that are part of the therapy cocktail could be very promising. You are basically finding out the market for the concept and figuring out what questions about which drugs need to be answered.”
They had good results from phase one of the NCI study, and have been invited to submit a phase two application. The next step after that is clinical trials.
“You can only get so far with basic research, but then it needs a massive financial boost to get into clinical trials with patients,” Griffin said. “The hope is that then a larger pharmaceutical company would join the effort because they have the major resources to put together the larger, randomized clinical trials needed to validate these things.”
Griffin has more than 25 years of experience as a radiation biologist, and his published research articles include those on experimental therapeutics and targeted radiation strategies for solid tumors, focusing on targeted delivery to the tumor vasculature and improvement of responses to radiation, thermal treatment, or chemotherapy. Some of his most notable recent publications are on using gold-cytokine nanoparticles to target the tumor microenvironment which can be used as a light-activated nanodrug.
“A lot of what we are doing involves not only nanoparticles, but also antibodies and peptides that preferentially bind to tumor cells or tumor blood vessels,” Griffin said. “We selectively deliver toxic drugs, so we have a differential between the tumor and normal tissues you don’t want targeted. There is a synergistic action to get maximum tumor kill while keeping effects to normal tissue at a minimum. The ultimate goal would be to develop a new standard of care for surgery and radiation therapy based on that approach which, after being tested and validated in clinical trials, would replace what is being done now. Everyone would benefit from this new approved standard.”
It can take a decade or longer to develop a new drug therapy and put it on the market. Griffin said Rejuvenix may be able to get approval faster since they are using FDA-approved drugs already being used in cancer patients and lipids that are also widely accepted.
“There may be a way to fast track Rejuvenix,” Griffin said. “The timeline related to this company effort might not be far away. It is nothing that extreme. We are hoping this could be approved for phase one safety trials in three to five years. When all hands are on deck and financing is in place, it can happen quickly.”
His entire radiation oncology department is moving to a new facility that includes a proton therapy center where charged particle beams can be delivered precisely to tumor volumes. This is a cooperative effort between UAMS, Baptist Health, Arkansas Children’s Hospital and Proton International.
We generally think of radiation as being bad but, being trained in radiation biology, Griffin is mostly interested in using novel features of different types of radiant energy to our advantage to deliver other drugs to cancer cells, and exploit what happens when tumors are also treated with other energy modalities such as ultrasound and lasers to heat and destroy the tumor.
“A lot of our treatment modalities when applied to a tumor change the tumor’s gene expression,” he said. “That creates new proteins to be expressed and those can be targeted by antibodies or peptides (small proteins).”
Griffin has also done considerable work in the area of anti-angiogenic/vascular biology of myeloma and breast cancer metastasis models and the development of PET imaging or photoacoustic detection of targeted drug delivery to these cancers.
Griffin graduated from St. Olaf college with a B.A. in biology and music in 1991, and then continued on to receive his PhD in Biophysical Sciences from the University of Minnesota in 1998. He has served as president and program chair for the Society for Thermal Medicine, which has an emphasis on nanotechnology for thermal treatments in a variety of modalities. He is also an associate senior editor for Technology in Cancer Research and Treatment and as associate editor for the International Journal of Radiation Oncology, Biology and Physics, as well as the journal Radiation Research.
Griffin’s first job out of college was in a radiation biology lab. He was attracted to radiation oncology because it is multidisciplinary and applied. It takes knowledge of all three: biology, physics and medicine.
Currently UAMS is working to get National Cancer Center designation, which would help attract more research dollars and enhance the reputation of UAMS.
“We hope this startup technology to deliver drugs more effectively will be a part of that story as a nationally-known NCI designated, comprehensive Cancer Center,” Griffin said.
Griffin says their 16 years in Arkansas have been great for him and his family. He grew up in Wisconsin where he enjoyed fishing and hunting, and has found fertile territory to pursue those hobbies in Arkansas. He and his wife, Amy Griffin, a teacher at Little Rock Christian Academy, have four children, one in junior high, one in high school, one in college and one college graduate.
“We spend as much time as we can on Greers Ferry fishing, camping and everything else,” Griffin said. “That has been our playground so far.”
For more information, visit:
Rejuvenix Technologies Wins NIH SBIR Award to Improve Chemotherapy Treatment,
UAMS, Arkansas Children’s, Baptist Health and Proton International Sign Letter of Intent to Build State’s First Proton Treatment Center,